TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4851	14776;14777;14778	chr2:178735895;178735894;178735893	chr2:179600622;179600621;179600620
N2AB	4534	13825;13826;13827	chr2:178735895;178735894;178735893	chr2:179600622;179600621;179600620
N2A	3607	11044;11045;11046	chr2:178735895;178735894;178735893	chr2:179600622;179600621;179600620
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-31
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1457
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/S	None	None	None	N	0.333	0.169	0.269558022972	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05
I/V	rs1286288159	None	None	N	0.133	0.065	0.353761421236	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	2.07125E-04	0
I/V	rs1286288159	None	None	N	0.133	0.065	0.353761421236	gnomAD-4.0.0	4.05984E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61483E-06	4.69748E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.1602	likely_benign	0.1447	benign	-2.738	Highly Destabilizing	0.002	N	0.414	neutral	None	None	None	None	N
I/C	0.3264	likely_benign	0.2903	benign	-2.024	Highly Destabilizing	0.245	N	0.547	neutral	None	None	None	None	N
I/D	0.4771	ambiguous	0.3749	ambiguous	-3.339	Highly Destabilizing	0.009	N	0.503	neutral	None	None	None	None	N
I/E	0.4153	ambiguous	0.3422	ambiguous	-3.118	Highly Destabilizing	0.009	N	0.489	neutral	None	None	None	None	N
I/F	0.1145	likely_benign	0.1004	benign	-1.611	Destabilizing	None	N	0.24	neutral	D	0.582442759	None	None	N
I/G	0.2877	likely_benign	0.2508	benign	-3.26	Highly Destabilizing	None	N	0.482	neutral	None	None	None	None	N
I/H	0.2516	likely_benign	0.2014	benign	-2.776	Highly Destabilizing	0.245	N	0.581	neutral	None	None	None	None	N
I/K	0.3065	likely_benign	0.2387	benign	-2.115	Highly Destabilizing	0.009	N	0.495	neutral	None	None	None	None	N
I/L	0.1	likely_benign	0.0899	benign	-1.213	Destabilizing	0.001	N	0.394	neutral	D	0.558110647	None	None	N
I/M	0.0932	likely_benign	0.0907	benign	-1.207	Destabilizing	0.108	N	0.484	neutral	D	0.638604987	None	None	N
I/N	0.1348	likely_benign	0.1135	benign	-2.485	Highly Destabilizing	0.017	N	0.528	neutral	D	0.535674002	None	None	N
I/P	0.8833	likely_pathogenic	0.8181	pathogenic	-1.706	Destabilizing	0.044	N	0.575	neutral	None	None	None	None	N
I/Q	0.2784	likely_benign	0.2282	benign	-2.344	Highly Destabilizing	0.044	N	0.615	neutral	None	None	None	None	N
I/R	0.2113	likely_benign	0.162	benign	-1.803	Destabilizing	0.044	N	0.589	neutral	None	None	None	None	N
I/S	0.0889	likely_benign	0.082	benign	-3.1	Highly Destabilizing	None	N	0.333	neutral	N	0.390364188	None	None	N
I/T	0.1004	likely_benign	0.0971	benign	-2.748	Highly Destabilizing	None	N	0.284	neutral	N	0.483973515	None	None	N
I/V	0.0684	likely_benign	0.0683	benign	-1.706	Destabilizing	None	N	0.133	neutral	N	0.505965516	None	None	N
I/W	0.5925	likely_pathogenic	0.5081	ambiguous	-2.086	Highly Destabilizing	0.788	D	0.602	neutral	None	None	None	None	N
I/Y	0.2704	likely_benign	0.2269	benign	-1.85	Destabilizing	0.022	N	0.545	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.